Biophotonics Winter School 2007
Lecture 2: Biodetection using silicon
photonic bandgap devices and other
silicon-based approaches
Philippe M. Fauchet
University of Rochester
Supported in part by the National Science
Foundation, the Infotonics Center of Excellence,
and the Center for Future Health
1
Yesterday’s talk
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Long-Term Goal
Materials Science of Porous Silicon
Sensing Principle using Microcavities
Examples of Biosensing
Ultimate Performance of these Biosensors
Futuristic Application
2
Today’s Talk Organization
• Ultimate performance of 1-D microcavities
• Futuristic application of these microcavities
• 2-D microcavities for single object detection
• Porous silicon retrofit to surface plasmon
resonance
• Imaging reflectometry sensor
• A new pre-concentration device
3
Biology Meets Nanoscale Silicon
Water
Glucose Antibody
10-1
In nanometer
1
nm
10
Virus
Bacteria
102
103
µm
Cancer
Cell
104
Tennis Ball
Fruit Fly
105
106
107
108
cm
Chip
4
Index of Refraction of Porous Silicon
The refractive index is a
function of:
refractive index of
silicon
refractive index inside
the pores
n-void=1
n-void=1.3
3.5
Effective index
neff
porosity
4
3
2.5
2
1.5
1
0
0
20
0.2
40
0.4
60
0.6
80
0.8
100
1
Porosity (%)
Porosity
(%)
5
Sensing Principle
Internal
surface
modification
Exposed to
species
n +n
n
11
Reflectivity
0.8
0.8
0.6
0.6
0.4
0.4
0.2
0.2
00
0.6
0.6
0.7
0.7
0.8
0.8
Wavelength (mm)
0.9
0.9
1
1
Red shift
Specific
binding
6
E. coli Cells from Culture
EPEC
JM 109
w/ Intimin
w/o Intimin
Red shift (nm)
6
5
No false positive
4
3
2
1
0
Tir-Intimin
1
No Tir-Intimin
2
Tir-JM108
3
No Tir-JM109
4
H. Ouyang, L. DeLouise, B.L. Miller and P.M. Fauchet,
Anal. Chem. 79, 1502-1506 (2007)
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Detailed Analysis of
Performance
8
Optimum Design Considerations
large overlap between the field inside the microcavity and
the analyte
Field confinement
in 1-D Microcavity
λ/n ~ 400 nm
6
1
λ(nm)
5
4
3
2
1
0
0
1.002
1.004
1.006
1.008
1.01
npore
Much better than microring cavity using evanescent field λ/n ~ 33 nm
J. Scheuer et al., Opt. Lett. 29, 2641 (2004).
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Filtering Unwanted Objects
Larger pores
Smaller pores
200 nm
10
Insensitivity to Surface “Dirt”
1
Reflectivity
0.8
0.6
0.4
0.2
0
0.6
0.7
0.8
0.9
1
Wavelength (mm)
11
Nanostructures and Sensitivity
(Simulation)
n
n
n n
n
n
n
n
L
8
Red shift (nm)
7
6
L=0.3 nm
5
4
3
2
1
0
0
50
100
Pore diameter (nm)
150
200
12
Nanostructures and Sensitivity
(Simulation)
120 nm pores
Sensitivity:
L
~50 pg/mm2
20 nm pores
Sensitivity:
~15 pg/mm2
8
L=1 nm
Red shift (nm)
7
L=0.7nm
6
L=0.5nm
5
L=0.3 nm
4
L=0.1 nm
3
L=0.05 nm
2
1
0
0
50
100
Pore diameter (nm)
150
200
13
H. Ouyang et al, Adv. Funct.
Mater.15, 1851 (2005)
Nanostructures and Sensitivity
(Experiment)
Glutaraldehyde
3-Aminopropyltriethoxysilane
+
0.7 nm
0.8 nm
(measured by ellipsometry on planar surface)
80
Red shift (nm)
70
60
50
40
L = 1.5 nm
30
20
10
L = 0.7 nm
0
0
50
100
150
200
Pore diameter (nm)
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H. Ouyang, C.C. Striemer, and P.M. Fauchet, Appl. Phys. Lett. 88, 163108 (2006)
6
Annealing temperature
900°C in O2
4
600°C in O2
900°C in N2
2
800°C in N2
0
700°C in N2
300°C in N2
-2
as-anodized
-4
20
Oxide thickness
Reflectance Blueshift (nm)
Possible problem: temperature sensitivity
40
60
80
100
120
Ambient Temperature (°C)
S.M. Weiss et al, Appl. Phys. Lett. 83, 1980 (2003)
15
Futuristic Application
16
The smart bandage
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A small step toward a smart bandage
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First Step Toward a Smart Bandage
J&J Nu-Gel Sheet
Contact lamination
Sensor in Air
Sensor in Gel
3 days
1 yr
120
% Reflection
100
80
~150 nm
red shift
60
40
20
0
600
650
700
750
800
850
900
950
wavelength (nm)
Withstand repeated dehydration / rehydration cycles
Sensitive even when mounted to gel
L. DeLouise et al. Adv. Mater. 17, 2199 (2005)
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First Step Toward a Smart Bandage
L. DeLouise et al., Adv. Mater. 17, 2199 (2005)
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Conclusions (1-D)
• 1D microcavities can be used as highly
sensitive optical label-free sensors
• Silicon 1-D microcavity biosensors with
different nanostructures have been
fabricated
• Sensitivity results validate the model
• The devices have been used for detecting
DNA segments, entire DNA strands, proteins,
and bacteria
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2-D Microcavities for Single
Object Detection
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2-D PBG Microcavity on SOI
- Silicon
e
- Silicon Dioxide
e
- E-beam Photoresist
Initial SOI wafer
Oxide Mask
Growth
Spin on
Resist
E-beam
lithography
Develop
Pattern
transfer
RIE etching
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Experimental setup (waveguide)
smaller
or
larger
hole
Polarizer
Tunable laser
1440~1590nm
TE
Polarization
controller
Sample
Detector
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Experimental Demonstration
Glutaraldehyde
BSA
100
(b)
(a)
(c)
Transmission (a.u.)
80
60
40
20
0
1584
1585
1586
1587
wavelength (nm)
1588
1589
Exposure to Glutaraldehyde, then BSA
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Comparison with theory
Detection Limit using the current devices:
~2 fg for complete device, ~ 0.05 fg in defect only
M. Lee and P.M. Fauchet, submitted to Opt. Express (2007)
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Single Biomolecule Detection
12
data
) 10
m
n
t
8
(f
i

h 6
s
d 4
e
R
1
2
- e-
Shift (nm)
Fit using e-
2
0
0
50
100
150
200
Molecule Diameter (nm)
Diameter (nm)
250
300
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Single particle detection
Transmission (a.u.)
100
80
60
40
20
0
1495
1500
1505
wavelength (nm)
Wavelength (nm)
1510
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Porous Silicon Retrofit to
Surface Plasmon Resonance
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Evanescent Wave-based Optical Sensors
Limitation: biomolecules exposed to exponentially
decaying E-field
prism
q
gold
Label-free surface
plasmon resonance sensor
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VANDERBILT University
WEISS GROUP
Porous Silicon Biosensors
Advantage: increased overlap of biomolecules
and peak E-field
Air
Lower index porous silicon cladding
Porous silicon
waveguide sensor
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VANDERBILT University
WEISS GROUP
Porous Silicon Waveguide Sensor
NEW PLATFORM
FOR BIOSENSING
Prism
Reflectance (%)
q
70
60
50
40
30
20
35
Air gap
n
36
37
38
39
Internal angle (degree)
High porosity
porous silicon
n ~ 1.62
Crystalline silicon substrate
VANDERBILT University
Low porosity
porous silicon
n ~ 2.17 + n
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WEISS GROUP
VANDERBILT University
WEISS GROUP
Theoretical Comparison
PSi WG
SPR
1.0
empty
Shift = 0.011˚
Reflectance
biomolecules
0.8
biomolecules
0.6
0.4
0.2
0.0
50.24
PSi WG
Shiftbiomolecules
= 0.075˚
50.28
50.32
50.36
Angle of Incidence (degrees)
~100-fold enhancement over SPR
33
J. J. Saarinen, S. M. Weiss, P. M. Fauchet, and J. E. Sipe, Optics Express 13, 3754 (2005)
VANDERBILT University
WEISS GROUP
DNA Detection (specific binding)
Reflectance (%)
70
60
GA
50
Silane
40
37
Probe
38
Target
39
Coupling Angle (degrees)
24-base pair DNA oligos
50 mM concentration detected
G. Rong and S. M. Weiss, Proc. of SPIE 6477, in press (2007)
1. Thermal oxidation
2. Aminosilane
3. Glutaraldehyde
4. Probe DNA
5. Target DNA
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Biodetection by
Reflectometry Imaging
35
Reflectometry Biosensor
Concept – The reflectivity from a nearly perfect AR coating is
extremely sensitive to nanoscale surface modifications (ex.
target binding)
36
Label-free Arrayed Imaging Reflectometry
A dense array of sensing spots can be imaged rapidly
Concept:
Commercialization:
J. Lu et al., Anal. Chem. 76, 4416 (2004)
Pathologics
37
Dynamic range and sensitivity
SPR
limit
Demonstrated intimin detection range: 10 pM to > 1 mM
Mace, C. R.; Striemer, C. C.; Miller, B. L.,
Anal. Chem. 78, 5578 (2006)
38
Filtration and Pre-Concentration
Demonstration:
C.C. Striemer et al., Nature 445, 749-753 (February 2007)
Commercialization:
SiMPore Inc.
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Ultrafiltration membranes
Conventional
Ideal
40
Membrane fabrication
41
Pore size control
• Pore morphology strong function of RTP
temperature
cutoff
cutoff
• Increasing temperature:
–larger pores
–higher porosity
cutoff
42
Pnc-Si membranes
• Buffered oxide etch – complementary high-contrast etch
pnc-Si/SiO2
sandwich
43
7 nm pnc-Si
The membranes are strong
0 PSI
3 PSI
6 PSI
12 PSI
15 PSI
200 mm
9 PSI
15 nm thickness
Elastic deformation without rupture
44
Molecular separations
45
Separation based on size
Free
Diffusion
Pnc-Si membranes are highly effective in separating
small molecules from proteins
46
Dye transport rate comparison
porosity = 0.2%
The diffusion rate of dye through pnc-Si is 10X that of a
commercial dialysis membrane with 50 kDa cutoff
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Official Conclusion
Many silicon-based biosensing platforms
are under development
Start-up companies have been created
to commercialize them
There is a need for further scientific and
technological breakthroughs
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Real Conclusion
So, join the field !!!
Where else can you have fun
(for sure) and make money
(maybe) at the same time ????
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